S-EPMC10398545 - Moderate-Intensity Statin With Ezetimibe Combination Therapy vs High-Intensity Statin Monotherapy in Patients at Very High Risk of Atherosclerotic Cardiovascular Disease: A Post Hoc Analysis From the RACING Randomized Clinical Trial. - OmicsDI

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Moderate-Intensity Statin With Ezetimibe Combination Therapy vs High-Intensity Statin Monotherapy in Patients at Very High Risk of Atherosclerotic Cardiovascular Disease: A Post Hoc Analysis From the RACING Randomized Clinical Trial.

ABSTRACT:

Importance

High-intensity statin is strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice.

Objective

To evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD.

Design, setting, and participants

This was a post hoc analysis of the Randomized Comparison of Efficacy and Safety of Lipid Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease (RACING) open-label, multicenter, randomized clinical trial. The study was conducted from February 2017 to December 2018 at 26 centers in Korea. Study participants included patients with documented ASCVD. Data were analyzed from April to June 2022.

Interventions

Patients were randomly assigned to moderate-intensity statin with ezetimibe (rosuvastatin, 10 mg, with ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). Patients at VHR for ASCVD were defined according to the 2018 American Heart Association/American College of Cardiology guidelines.

Main outcomes and measures

The primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke.

Results

A total of 3780 patients (mean [SD] age, 64 [10] years; 2826 male [75%]) in the RACING trial, 1511 (40.0%) were categorized as VHR, which was associated with a greater occurrence of the primary end point (hazard ratio [HR], 1.42; 95% CI, 1.15-1.75). There was no significant difference in the primary end point between those who received combination therapy and high-intensity statin monotherapy among patients with VHR disease (11.2% vs 11.7%; HR, 0.96; 95% CI, 0.71-1.30) and non-VHR disease (7.7% vs 8.7%; HR, 0.88; 95% CI, 0.66-1.18). The median low-density lipoprotein cholesterol (LDL-C) level was significantly lower in the combination therapy group than in the high-intensity statin group (VHR, 1 year: 57 [47-71] mg/dL vs 65 [53-78] mg/dL; non-VHR, 1 year: 58 mg/dL vs 68 mg/dL; P < .001). Furthermore, in both the VHR and non-VHR groups, combination therapy was associated with a significantly greater mean change in LDL-C level (VHR, 1 year: -19.1 mg/dL vs -10.1 mg/dL; 2 years: -22.3 mg/dL vs -13.0 mg/dL; 3 years: -18.8 mg/dL vs -9.7 mg/dL; non-VHR, 1 year: -23.7 mg/dL vs -12.5 mg/dL; 2 years: -25.2 mg/dL vs -15.1 mg/dL; 3 years: -23.5 mg/dL vs -12.6 mg/dL; all P < .001) and proportion of patients with LDL-C level less than 70 mg/dL (VHR, 1 year: 73% vs 58%; non-VHR, 1 year: 72% vs 53%; P < .001). Discontinuation or dose reduction of the lipid-lowering drug due to intolerance occurred less frequently in the combination therapy group (VHR, 4.6% vs 7.7%; P = .02; non-VHR, 5.0% vs 8.7%; P = .001).

Conclusions and relevance

Results suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD.

Trial registration

ClinicalTrials.gov Identifier: NCT03044665.

SUBMITTER: Lee SJ

PROVIDER: S-EPMC10398545 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Moderate-Intensity Statin With Ezetimibe Combination Therapy vs High-Intensity Statin Monotherapy in Patients at Very High Risk of Atherosclerotic Cardiovascular Disease: A Post Hoc Analysis From the RACING Randomized Clinical Trial.

Lee Seung-Jun SJ Cha Jung-Joon JJ Choi Woong Gil WG Lee Wang-Soo WS Jeong Jin-Ok JO Choi Seonghoon S Cho Yoon-Haeng YH Park Woojung W Yoon Chang-Hwan CH Lee Yong-Joon YJ Hong Sung-Jin SJ Ahn Chul-Min CM Kim Byeong-Keuk BK Ko Young-Guk YG Choi Donghoon D Hong Myeong-Ki MK Jang Yangsoo Y Hong Soon Jun SJ Kim Jung-Sun JS

JAMA cardiology 20230901 9

<h4>Importance</h4>High-intensity statin is strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice.<h4>Objective</h4>To evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD.<h4>Design, setting, and participants</h4>This was a post hoc analysis of the Randomized Comparison of ...[more]

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Project description:BackgroundDespite widespread use of high-intensity statin monotherapy, achieving target LDL-C levels and reducing cardiovascular events in patients with or at high risk of developing ASCVD remains challenging. Our study measured the effects of low/moderate-intensity statins and ezetimibe combination therapy compared to high-dose statin monotherapy on major adverse cardiovascular events (MACEs) and coronary atherosclerotic plaque reduction.MethodsWe searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL register of trials for studies comparing the combination therapy to high-intensity statin monotherapy in terms of MACEs and coronary atherosclerotic plaque reduction. The primary outcome was a composite of cardiovascular death or major cardiovascular events (MI, HF, Revascularization, or non-fatal stroke). Other outcomes included other MACEs, lipid-lowering efficacy, and safety outcomes. A protocol was registered to PROSPERO under registration number [CRD42024545807].Results15 studies encompassing 251,450 participants were included in our meta-analysis. In our pooled analysis of observational studies, combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76, CI 95% [0.73, 0.80]), cardiovascular death (HR = 0.80, CI 95% [0.74, 0.88]), all-cause death (HR = 0.84, CI 95% [0.78, 0.91]), and non-fatal stroke (HR = 0.81, CI 95% [0.75, 0.87]). However, the pooled analysis of RCTs did not demonstrate a statistically significant difference between both arms concerning clinical endpoints. Combination therapy had a higher number of patients with LDL-C < 70 mg/dL (RR = 1.27, CI 95% [1.21, 1.34]), significantly lowered LDL-C (MD = -7.95, CI 95% [-10.02, -5.89]) and TC (MD = -26.77, CI 95% [-27.64, -25.89]) in the pooled analysis of RCTs. In terms of safety, the combination therapy lowered muscle-related adverse events (RR = 0.52, CI 95% [0.32, 0.85]) and number of patients with liver enzyme elevation (RR = 0.51, CI 95% [0.29, 0.89]) in the pooled analysis of RCTs and was associated with lower rates of new-onset diabetes (HR = 0.80, CI 95% [0.74, 0.87]) in the pooled analysis of observational studies.ConclusionEvidence from RCTs indicates that low/moderate statin therapy in combination with ezetimibe has a superior lipid-lowering effect and reduces side effects compared to high-dose statins. Observational studies suggest improved clinical outcomes but need to be corroborated by large, outcomes-powered RCTs over longer follow-up periods.

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